DOCSLIB.ORG

Role of 15-Lipoxygenase/15-Hydroxyeicosatetraenoic Acid in Hypoxia-Induced Pulmonary Hypertension

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Role of 15-Lipoxygenase/15-Hydroxyeicosatetraenoic Acid in Hypoxia-Induced Pulmonary Hypertension J Physiol Sci (2012) 62:163–172 DOI 10.1007/s12576-012-0196-9 REVIEW Role of 15-lipoxygenase/15-hydroxyeicosatetraenoic acid in hypoxia-induced pulmonary hypertension Daling Zhu • Yajuan Ran Received: 29 September 2011 / Accepted: 25 January 2012 / Published online: 14 February 2012 Ó The Physiological Society of Japan and Springer 2012 Abstract Pulmonary arterial hypertension (PAH) is a Introduction rare disease with a complex aetiology characterized by elevated pulmonary artery resistance, which leads to right Pulmonary hypertension (PH) is a severe and frequently heart ventricular afterload and ultimately progressing to fatal disease characterized by elevated mean pulmonary right ventricular failure and often death. In addition to arterial (PA) pressure greater than 25 mmHg at rest or other factors, metabolites of arachidonic acid cascade play greater than 30 mmHg with exercise [1], and which con- an important role in the pulmonary vasculature, and dis- tributes to the morbidity and mortality of adult and pedi- ruption of signaling pathways of arachidonic acid plays a atric patients with various lung and heart diseases. central role in the pathogenesis of PAH. 15-Lipoxygenase According to the Venice Classification of Pulmonary (15-LO) is upregulated in pulmonary artery endothelial Hypertension in 2003, PH is currently classified into five cells and smooth muscle cells of PAH patients, and its categories as listed in Table 1. Importantly, many of these metabolite 15-hydroxyeicosatetraenoic acid (15-HETE) in diseases or conditions are associated with persistent or particular seems to play a central role in the contractile intermittent hypoxia, either globally or regionally, within machinery, and in the initiation and propagation of cell confined areas of the lung [2]. The acute hypoxia-induced proliferation via its effects on signal pathways, mitogens, pulmonary vasoconstriction (HPV) is an important mech- and cell cycle components. Here, we focus on our impor- anism that aids in matching ventilation with perfusion by tant research into the role played by 15-LO/15-HETE, directing blood flow from poorly ventilated regions of the which promotes a proliferative, antiapoptotic, and vaso- lung to areas with normal or relatively high ventilation. constrictive physiological milieu leading to hypoxic pul- Although acute HPV benefits gas exchange and maximizes monary hypertension. oxygenation of venous blood in the pulmonary artery, sustained HPV or chronic exposure to hypoxia is a major Keywords Hypoxic pulmonary hypertension Á cause for the elevated pulmonary vascular resistance and 15-Lipoxygenase Á 15-Hydroxyeicosatetraenoic acid Á pulmonary arterial remodeling (PAR) in patients with Vasoconstriction Á Remodeling pulmonary arterial hypertension (PAH) associated with hypoxic cardiopulmonary diseases [3]. Vascular remodel- ing is characterized largely by medial hypertrophy and hyperplasia due to enhanced vascular smooth muscle cell D. Zhu (&) (VSMC) proliferation or attenuated apoptosis and endo- College of Pharmacy, Harbin Medical University-Daqing, thelial cell over-proliferation [4, 5]. However, the mecha- No. 1 Xinyang Street, High-tech Zone, Daqing 163319, Heilongjiang, People’s Republic of China nism of pulmonary vascular remodeling (PVR) and e-mail: [email protected] pulmonary hypertension is still unknown. The arachidonic acid cascade plays a vital role in D. Zhu Á Y. Ran homeostasis of the endothelium and VSMCs, and has been Biopharmaceutical Key Laboratory of Heilongjiang Province, 157 Baojian Road, Nangang District, Harbin 150081, observed in dysregulation of downstream pathways of Heilongjiang, People’s Republic of China arachidonic acid in patients with PAH and in animal 123 164 J Physiol Sci (2012) 62:163–172 Table 1 Clinical classification of pulmonary hypertension models. More and more biological data suggest that ara- Venice Classification of Pulmonary Hypertension (2003) chidonic acid metabolites of lipoxygenases (LOs) play pivotal roles in the pathological development of PAH. LOs 1. Pulmonary arterial hypertension (PAH) are a family of non-heme iron-containing enzymes which 1.1. Idiopathic (IPAH) dioxygenate polyunsaturated fatty acids to hydroperoxyl 1.2. Familial (FPAH) metabolites. As shown in Table 2, LOs mainly include 1.3. Associated with (APAH) four isoforms, 5-lipoxygenase (5-LO) [6], 8-lipoxygenase 1.3.1. Collagen vascular disease (8-LO) [7, 8], 12-lipoxygenase (12-LO) [9], and 1.3.2. Congenital systemic-to-pulmonary shunts 15-lipoxygenase (15-LO) [10], which correspond to the 1.3.3. Portal hypertension carbon position of arachidonic acid oxygenation, whereas 1.3.4. HIV infection 8-LO was not found to be expressed in human tissues. LOs 1.3.5. Drugs and toxins are involved in biosynthesis of vasoactive mediators, 1.3.6. Other (thyroid disorders, glycogen storage disease, Gaucher growth factors, adhesion molecules, and cytokines [10–12], disease, hereditary hemorrhagic telangiectasia, and hence are important targets for the atherogenesis, hemoglobinopathies, myeloproliferative disorders, splenectomy) vasoconstriction, and vascular remodeling. Moreover, 1.4. Associated with significant venous or capillary involvement LOs-derived compounds impact the metabolic character- 1.4.1. Pulmonary veno-occlusive disease (PVOD) istics of vascular cells, particularly those of endothelial 1.4.2. Pulmonary capillary hemangiomatosis (PCH) cells (EC) and smooth muscles cells (SMC) [13, 14]. In our 1.5. Persistent pulmonary hypertension of the newborn laboratory, we have reported that 15-LO/15-HETE played 2. Pulmonary hypertension with left heart disease an important role in hypoxic pulmonary hypertension 2.1. Left-sided atrial or ventricular heart disease (HPH). Therefore, this review is intended to provide a 2.2. Left-sided valvular heart disease comprehensive overview of the effect of 15-LO/15-HETE 3. Pulmonary hypertension associated with lung diseases and/or on HPH, and also to propose underlying the important hypoxemia aspects of 5-LO and 12-LO in PAH. 3.1. Chronic obstructive pulmonary disease 3.2. Interstitial lung disease 3.3. Sleep-disordered breathing Basic properties of LOs 3.4. Alveolar hypoventilation disorders 3.5. Chronic exposure to high altitude Two distinct types of 15-LO have been identified in 3.6. Developmental abnormalities humans: reticulocyte type of 15-LO-1 [15] and epidermis 4. Pulmonary hypertension owing to chronic thrombotic and/or type of 15-LO-2 [16]. 15-LO-1 was initially discovered in a embolic disease rabbit reticulocytes mass at a 75-kD, single-polypeptide 4.1. Thromboembolic obstruction of proximal pulmonary arteries chain [17]; the enzyme has a two-domain structure [18] 4.2. Thromboembolic obstruction of distal pulmonary arteries with one non-heme iron per molecule. 15-LO-2 was sub- 4.3. Nonthrombotic pulmonary embolism (tumor, parasites, sequently identified, and its expression has been reported in foreign material) human prostate, skin, and cornea [17]. Both enzymes con- 5. Miscellaneous: sarcoidosis, histiocytosis X, lymphangiomatosis, vert arachidonic acid to 15-hydroperoxyeicosatetraenoic compression of pulmonary vessels (adenopathy, tumor, fibrosing mediastinitis) acid (15(S)-HPETE). 15(S)-HPETE is unstable and can be reduced by peroxidases to the corresponding Table 2 Basic properties of LOs Gene name Alternative nomenclature Predominant enzyme products Main distribution ALOX15 15-LOX-1 15(S)-HPETE, 15(S)-HETE Reticulocyte, eosinophils, bronchial epithelial cells 15-LOX-2 15(S)-HPETE, 15(S)-HETE Prostate, skin, lung, cornea ALOX12 Platelet-type lipoxygenase 12 12(S)-HPETE, 12(S)-HETE In various cell types Epidermis-type lipoxygenase 12 12(R)-HPETE, 12(R)-HETE In various cell types Leukocyte-type lipoxygenase 12 12(S)-HPETE, 12(S)-HETE In various cell types ALOX8 8-LOX 8(S)-HPETE, 8(S)-HETE Only in mice and rats tissues ALOX5 5-LOX 5-HETE, leukotrienes In various cell types 123 J Physiol Sci (2012) 62:163–172 165 15-hydroxyeicosatetraenoic acid (15-HETE), but they share 15-HETE inhibits the activity of 5-LO and LT production only 40% amino acid homology, and there are two major by neutrophils [32–34]. The expression of 15-LO induced differences between the isozymes. The first difference is by interleukin (IL)-4 in monocytes significantly decreased that 15-LO-1 converts AA to 15(S)-HPETE (90%) and the LTB4 expression [35]. 15-HETE can inhibit neutrophil lesser amounts of 12(S)-HPETE (10%), whereas 15-LO-2 migration across cytokine-activated (interleukin-1 beta or produces exclusively 15(S)-HPETE [17]. The second dif- tumor necrosis factor-alpha) endothelium [36]. Transfec- ference is that, although both arachidonic acid and linoleic tion of rat kidney with human 15-LO can suppress acid are preferred substrates for 15-LO-1, only arachidonic inflammation [37]. According to these studies, the in vivo acid is a substrate for 15-LO-2 [19, 20]. activity of 15-LO/15-HETE may be regarded as a protec- The human 5-LO consists of 673 amino acids and a non- tive response to limit or reverse inflammatory symptoms heme iron, and the sequence is highly homologous with and to maintain basic cell function [38]. those of other mammalian LOs and soybean 15-LO [21]. Also, it has been found that 15-LO is implicated in 5-LO catalyzes conversion of arachidonic acid to leukotri- the maturation of rabbit reticulocytes by inhibiting ene (LT) A4, which can be subsequently converted into the mitochondria degradation [39–41]. 15-HETE improves the potent chemoattractant LTB4, or into cysteinyl leukotrienes proliferation
Load more

Recommended publications
  • Eicosanoids in Carcinogenesis
    4open 2019, 2,9 © B.L.D.M. Brücher and I.S. Jamall, Published by EDP Sciences 2019 https://doi.org/10.1051/fopen/2018008 Special issue: Disruption of homeostasis-induced signaling and crosstalk in the carcinogenesis paradigm “Epistemology of the origin of cancer” Available online at: Guest Editor: Obul R. Bandapalli www.4open-sciences.org REVIEW ARTICLE Eicosanoids in carcinogenesis Björn L.D.M. Brücher1,2,3,*, Ijaz S. Jamall1,2,4 1 Theodor-Billroth-Academy®, Germany, USA 2 INCORE, International Consortium of Research Excellence of the Theodor-Billroth-Academy®, Germany, USA 3 Department of Surgery, Carl-Thiem-Klinikum, Cottbus, Germany 4 Risk-Based Decisions Inc., Sacramento, CA, USA Received 21 March 2018, Accepted 16 December 2018 Abstract- - Inflammation is the body’s reaction to pathogenic (biological or chemical) stimuli and covers a burgeoning list of compounds and pathways that act in concert to maintain the health of the organism. Eicosanoids and related fatty acid derivatives can be formed from arachidonic acid and other polyenoic fatty acids via the cyclooxygenase and lipoxygenase pathways generating a variety of pro- and anti-inflammatory mediators, such as prostaglandins, leukotrienes, lipoxins, resolvins and others. The cytochrome P450 pathway leads to the formation of hydroxy fatty acids, such as 20-hydroxyeicosatetraenoic acid, and epoxy eicosanoids. Free radical reactions induced by reactive oxygen and/or nitrogen free radical species lead to oxygenated lipids such as isoprostanes or isolevuglandins which also exhibit pro-inflammatory activities. Eicosanoids and their metabolites play fundamental endocrine, autocrine and paracrine roles in both physiological and pathological signaling in various diseases. These molecules induce various unsaturated fatty acid dependent signaling pathways that influence crosstalk, alter cell–cell interactions, and result in a wide spectrum of cellular dysfunctions including those of the tissue microenvironment.
    [Show full text]
  • University of California, San Diego
    UNIVERSITY OF CALIFORNIA, SAN DIEGO A Lipidomic Perspective on Inflammatory Macrophage Eicosanoid Signaling A Thesis submitted in partial satisfaction of the requirements for the degree Doctor of Philosophy in Chemistry by Paul Christopher Norris Committee in charge: Professor Edward A. Dennis, Chair Professor Pieter C. Dorrestein Professor Partho Ghosh Professor Christopher K. Glass Professor Michael J. Sailor 2013 The Dissertation of Paul Christopher Norris is approved, and it is acceptable in quality and form for publication on microfilm and electronically: Chair University of California, San Diego 2013 iii DEDICATION To my parents, Darrell and Kathy, for always allowing me to think (and choose) for myself. iv TABLE OF CONTENTS Signature page ............................................................................................................................ iii Dedication .................................................................................................................................. iv Table of contents ......................................................................................................................... v List of symbols and abbreviations ........................................................................................... viii List of figures ............................................................................................................................. xi List of tables ............................................................................................................................
    [Show full text]
  • The Relationship Between Specialized Pro-Resolving Lipid Mediators, Morbid Obesity and Weight Loss After Bariatric Surgery
    www.nature.com/scientificreports OPEN The relationship between specialized pro‑resolving lipid mediators, morbid obesity and weight loss after bariatric surgery Fabian Schulte1,2,7, Abdul Aziz Asbeutah3,6,7, Peter N. Benotti4, G. Craig Wood4, Christopher Still4, Bruce R. Bistrian5, Markus Hardt1,2 & Francine K. Welty3* Obesity and diabetes are associated with chronic infammation. Specialized pro‑resolving lipid mediators (SPMs)—resolvins (Rv), protectins (PD) and maresins (MaR)—actively resolve infammation. Bariatric surgery achieves remission of diabetes, but mechanisms are unclear. We measured SPMs and proinfammatory eicosanoid levels using liquid chromatography‑tandem mass spectrometry in 29 morbidly obese subjects (13 with diabetes) and 15 nondiabetic, mildly obese subjects. Compared to the mildly obese, the morbidly obese had higher levels of SPMs—RvD3, RvD4 and PD1—and white blood cells (WBC) and platelets. Post‑surgery, SPM and platelet levels decreased in morbidly obese nondiabetic subjects but not in diabetic subjects, suggesting continued infammation. Despite similar weight reductions 1 year after surgery (44.6% vs. 46.6%), 8 diabetes remitters had signifcant reductions in WBC and platelet counts whereas fve non‑remitters did not. Remitters had a 58.2% decrease (p = 0.03) in 14‑HDHA, a maresin pathway marker; non‑remitters had an 875.7% increase in 14‑HDHA but a 36.9% decrease in MaR1 to a median of 0. In conclusion, higher levels of RvD3, PD1 and their pathway marker, 17‑HDHA, are markers of leukocyte activation and infammation in morbid obesity and diabetes and diminish with weight loss in nondiabetic but not diabetic subjects, possibly representing sustained infammation in the latter.
    [Show full text]
  • Serum Leukotriene Metabolism and Type I Hypersensitivity Reactions in Different Animal Species
    University of Montana ScholarWorks at University of Montana Graduate Student Theses, Dissertations, & Professional Papers Graduate School 1989 Serum leukotriene metabolism and Type I hypersensitivity reactions in different animal species Thulasi Sarojam Unnitan The University of Montana Follow this and additional works at: https://scholarworks.umt.edu/etd Let us know how access to this document benefits ou.y Recommended Citation Unnitan, Thulasi Sarojam, "Serum leukotriene metabolism and Type I hypersensitivity reactions in different animal species" (1989). Graduate Student Theses, Dissertations, & Professional Papers. 3533. https://scholarworks.umt.edu/etd/3533 This Thesis is brought to you for free and open access by the Graduate School at ScholarWorks at University of Montana. It has been accepted for inclusion in Graduate Student Theses, Dissertations, & Professional Papers by an authorized administrator of ScholarWorks at University of Montana. For more information, please contact [email protected]. Maureen and Mike MANSFIELD TJBRARY Copying allowed as provided under provisions of the Fair Use Section of the U.S. COPYRIGHT LAW, 1976. Any copying for commercial purposes or financial gain may be undertaken only with the author's written consent. MontanaUniversity of SERUM LEUKOTRIENE METABOLISM AND TYPE I HYPERSENSITIVITY REACTIONS IN DIFFERENT ANIMAL SPECIES By Thulasi Sarojam Unnithan M.B.B.S., Trivandrum Medical College, India, 1981 Presented in partial fulfillment of the requirements for the degree of Master of Science University of Montana, 1989 8^'an, Graduate School ($hL& . & Date UMI Number: EP34626 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent on the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted.
    [Show full text]
  • Ioi70902.Pdf
    ORIGINAL INVESTIGATION Montelukast, a Once-Daily Leukotriene Receptor Antagonist, in the Treatment of Chronic Asthma A Multicenter, Randomized, Double-blind Trial Theodore F. Reiss, MD; Paul Chervinsky, MD; Robert J. Dockhorn, MD; Sumiko Shingo, MS; Beth Seidenberg, MD; Thomas B. Edwards, MD; for the Montelukast Clinical Research Study Group Objectives: To determine the clinical effect of oral mon- Results: Montelukast improved airway obstruction telukast sodium, a leukotriene receptor antagonist, in asth- (forced expiratory volume in 1 second, morning and matic patients aged 15 years or more. evening peak expiratory flow rate) and patient-reported end points (daytime asthma symptoms, “as-needed” Design: Randomized, multicenter, double-blind, placebo- b-agonist use, nocturnal awakenings) (P,.001 com- controlled, parallel-group study. A 2-week, single- pared with placebo). Montelukast provided near- blind, placebo run-in period was followed by a 12- maximal effect in these end points within the first day week, double-blind treatment period (montelukast of treatment. Tolerance and rebound worsening of asthma sodium, 10 mg, or matching placebo, once daily at bed- did not occur. Montelukast improved outcome end points, time) and a 3-week, double-blind, washout period. including asthma exacerbations, asthma control days (P,.001 compared with placebo), and decreased periph- Setting/Patients: Fifty clinical centers randomly allo- eral blood eosinophil counts (P,.001 compared with pla- cated 681 patients with chronic, stable asthma to receive pla- cebo). The incidence of adverse events and discontinu- cebo or montelukast after demonstrating a forced expira- ations from therapy were similar in the montelukast and tory volume in 1 second 50% to 85% of the predicted value, placebo groups.
    [Show full text]
  • Strict Regio-Specificity of Human Epithelial 15-Lipoxygenase-2
    Strict Regio-specificity of Human Epithelial 15-Lipoxygenase-2 Delineates its Transcellular Synthesis Potential Abigail R. Green, Shannon Barbour, Thomas Horn, Jose Carlos, Jevgenij A. Raskatov, Theodore R. Holman* Department Chemistry and Biochemistry, University of California Santa Cruz, 1156 High Street, Santa Cruz CA 95064, USA *Corresponding author: Tel: 831-459-5884. Email: [email protected] FUNDING: This work was supported by the NIH NS081180 and GM56062. Abbreviations: LOX, lipoxygenase; h15-LOX-2, human epithelial 15-lipoxygenase-2; h15-LOX-1, human reticulocyte 15-lipoxygenase-1; sLO-1, soybean lipoxygenase-1; 5-LOX, leukocyte 5-lipoxygenase; 12-LOX, human platelet 12-lipoxygenase; GP, glutathione peroxidase; AA, arachidonic acid; HETE, hydoxy-eicosatetraenoic acid; HPETE, hydroperoxy-eicosatetraenoic acid; diHETEs, dihydroxy-eicosatetraenoic acids; 5-HETE, 5-hydroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 5-HPETE, 5-hydro peroxy-6E,8Z,11Z,14Z-eicosatetraenoic acid; 12-HPETE, 12-hydroperoxy-5Z,8Z,10E, 14Z-eicosatetraenoic acid; 15-HPETE, 15-hydroperoxy-5Z,8Z,10Z,13E- eicosatetraenoic acid; 5,15-HETE, 5S,15S-dihydroxy-6E,8Z,10Z,13E-eicosatetraenoic acid; 5,15-diHPETE, 5,15-dihydroperoxy-6E,8Z,10Z,13E-eicosatetraenoic acid; 5,6- diHETE, 5S,6R-dihydroxy-7E,9E,11Z,14Z-eicosatetraenoic acid; LTA4, 5S-trans-5,6- oxido-7E,9E,11Z,14Z-eicosatetraenoic acid; LTB4, 5S,12R-dihydroxy-6Z,8E,10E,14Z- eicosatetraenoic acid; LipoxinA4 (LxA4), 5S,6R,15S-trihydroxy-7E,9E,11Z,13E- eicosatetraenoic acid; LipoxinB4 (LxB4), 5S,14R,15S-trihydroxy-6E,8Z,10E,12E- eicosatetraenoic acid. Abstract Lipoxins are an important class of lipid mediators that induce the resolution of inflammation, and arise from transcellular exchange of arachidonic acid (AA)- derived lipoxygenase products.
    [Show full text]
  • Montelukast, a Leukotriene Receptor Antagonist, for the Treatment of Persistent Asthma in Children Aged 2 to 5 Years
    Montelukast, a Leukotriene Receptor Antagonist, for the Treatment of Persistent Asthma in Children Aged 2 to 5 Years Barbara Knorr, MD*; Luis M. Franchi, MD‡; Hans Bisgaard, MD§; Jan Hendrik Vermeulen, MDʈ; Peter LeSouef, MD¶; Nancy Santanello, MD, MS*; Theresa M. Michele, MD*; Theodore F. Reiss, MD*; Ha H. Nguyen, PhD*; and Donna L. Bratton, MD# ABSTRACT. Background. The greatest prevalence of baseline period. Patients had a history of physician-di- asthma is in preschool children; however, the clinical agnosed asthma requiring use of ␤-agonist and a pre- utility of asthma therapy for this age group is limited by defined level of daytime asthma symptoms. Caregivers a narrow therapeutic index, long-term tolerability, and answered questions twice daily on a validated, asthma- frequency and/or difficulty of administration. Inhaled specific diary card and, at specified times during the corticosteroids and inhaled cromolyn are the most com- study, completed a validated asthma-specific quality-of- monly prescribed controller therapies for young children life questionnaire. Physicians and caregivers completed a with persistent asthma, although very young patients global evaluation of asthma control at the end of the may have difficulty using inhalers, and dose delivery can study. be variable. Moreover, reduced compliance with inhaled Efficacy end points included: daytime and overnight therapy relative to orally administered therapy has been asthma symptoms, daily use of ␤-agonist, days without reported. One potential advantage of montelukast is the asthma, frequency of asthma attacks, number of patients ease of administering a once-daily chewable tablet; ad- discontinued because of asthma, need for rescue medica- ditionally, no tachyphylaxis or change in the safety pro- tion, physician and caregiver global evaluations of file has been evidenced after up to 140 and 80 weeks of change, asthma-specific caregiver quality of life, and pe- montelukast therapy in adults and pediatric patients ripheral blood eosinophil counts.
    [Show full text]
  • Phospholipase A2 Regulates Eicosanoid Class Switching During Inflammasome Activation
    Phospholipase A2 regulates eicosanoid class switching during inflammasome activation Paul C. Norrisa, David Gosselinb, Donna Reichartb, Christopher K. Glassb, and Edward A. Dennisa,1 Departments of aChemistry/Biochemistry and Pharmacology, and bCellular and Molecular Medicine, University of California, San Diego, La Jolla, CA 92093 Edited by Michael A. Marletta, The Scripps Research Institute, La Jolla, CA, and approved July 30, 2014 (received for review March 13, 2014) Initiation and resolution of inflammation are considered to be to initiate pathogenic killing, subsequent “class switching” to lipoxin tightly connected processes. Lipoxins (LX) are proresolution lipid (LX) formation by “reprogrammed” neutrophils inhibits additional mediators that inhibit phlogistic neutrophil recruitment and pro- neutrophil recruitment during self-resolving inflammatory resolu- mote wound-healing macrophage recruitment in humans via tion (9). The direct link between inflammatory commitment and potent and specific signaling through the LXA4 receptor (ALX). resolution mediated by eicosanoid signaling in macrophages One model of lipoxin biosynthesis involves sequential metabolism remains unclear from short-term vs. long-term priming, but the of arachidonic acid by two cell types expressing a combined trans- complete temporal changes and important interconnections cellular metabolon. It is currently unclear how lipoxins are effi- within the entire eicosadome are now demonstrated. ciently formed from precursors or if they are directly generated after receptor-mediated inflammatory commitment. Here, we pro- Results vide evidence for a pathway by which lipoxins are generated in We first primed immortalized macrophage-like cells (RAW264.7) macrophages as a consequence of sequential activation of toll-like with the TLR4 agonist Kdo2 lipid A (KLA) for various times and receptor 4 (TLR4), a receptor for endotoxin, and P2X7, a purinergic examined the effects on subsequent purinergic stimulated COX receptor for extracellular ATP.
    [Show full text]
  • Nutrition Bytes
    UCLA Nutrition Bytes Title Theories Presented in The Zone Permalink https://escholarship.org/uc/item/9pg2j7wk Journal Nutrition Bytes, 3(1) ISSN 1548-4327 Author Chang, Jeannie Publication Date 1997 Peer reviewed eScholarship.org Powered by the California Digital Library University of California "Easy -to -follow" diet plans appear each year to convince overweight Americans that there is finally a way to lose weight permanently. Barry Sears and Bill Lawren’s book, The Zone, is no exception; in fact, Sears’ book cover advertises that it is "a dietary road map to lose weight permanently, reset your genetic code, prevent disease, achieve maximum physical performance, [and] enhance mental productivity." But is this realistic? Can a diet really accomplish all of those tasks? After numerous searches through several databases, only two journal articles analyzing this diet plan surfaced, both warning readers about the misinformation contained in the book. There are definitely problems with Sears’ diet; for example, his daily caloric intake recommendation is dangerously low. Tufts University Diet and Nutrition Letter stated that they believed "[Sears was] confusing the near -euphoria he promises from following the Zone diet with lightheadedness from hunger" (3). Dr. Zamenhof, Associate Professor of Biological Ch emistry at UCLA said that it was probably due to an increased release of endorphins, enkephalins, and catecholamines. In addition, the information he provides regarding carbohydrate and fat metabolism, as well as insulin and glucagon secretion, are wrong. However, Sears also says that there is a direct relationship between insulin and glucagon with the synthesis of "good" eicosanoids (prostaglandin E1 and prostaglandin I2 and "bad" eicosanoids (prostaglandin E2, thromboxanes, and leukotrienes).
    [Show full text]
  • Leukotriene Modifiers (Accolate®, Singulair®, Zileuton®)
    Leukotriene Modifiers (Accolate®, Singulair®, Zileuton®) What are They? Leukotriene modifiers reduce swelling and inflammation in the airways to prevent asthma symptoms. You may not notice a change in your asthma symptoms for one to two week, after starting to use them. • These medicines will not stop a sudden asthma attack. Albuterol should be used for sudden asthma attacks. • Only regular daily use of the leukotriene modifiers will prevent asthma symptoms. • It is important that you do not stop or decrease the dose of these medications without contacting your doctor. How should they be used? • Zafirlukast (Accolate®) is a tablet that is taken by mouth twice a day on an empty stomach (1 hour before you eat or 2 hours after you eat). It is very important to take this medicine on an empty stomach. o Zafirlukast must be taken every day even if you don’t have asthma symptoms. If you forget to take your dose on time, do not take twice as much the next time. Take the regularly scheduled dose as soon as you remember, then get back to your regular schedule. o Side effects . Zafirlukast (Accolate®) causes very few side effects. Some people may have headaches, nausea, or diarrhea. Although these side effects are quite uncommon, it is important for you to let your doctor know if you are experiencing any of these while taking zafirlukast. • Montelukast (Singulair®) o A tablet that is taken once a day at nighttime. o You can take Montelukast with or without food. o Montelukast must be taken every day even if you don’t have asthma symptoms.
    [Show full text]
  • Omega-3, Omega-6 and Omega-9 Fatty Acids
    Johnson and Bradford, J Glycomics Lipidomics 2014, 4:4 DOI: 0.4172/2153-0637.1000123 Journal of Glycomics & Lipidomics Review Article Open Access Omega-3, Omega-6 and Omega-9 Fatty Acids: Implications for Cardiovascular and Other Diseases Melissa Johnson1* and Chastity Bradford2 1College of Agriculture, Environment and Nutrition Sciences, Tuskegee University, Tuskegee, Alabama, USA 2Department of Biology, Tuskegee University, Tuskegee, Alabama, USA Abstract The relationship between diet and disease has long been established, with epidemiological and clinical evidence affirming the role of certain dietary fatty acid classes in disease pathogenesis. Within the same class, different fatty acids may exhibit beneficial or deleterious effects, with implications on disease progression or prevention. In conjunction with other fatty acids and lipids, the omega-3, -6 and -9 fatty acids make up the lipidome, and with the conversion and storage of excess carbohydrates into fats, transcendence of the glycome into the lipidome occurs. The essential omega-3 fatty acids are typically associated with initiating anti-inflammatory responses, while omega-6 fatty acids are associated with pro-inflammatory responses. Non-essential, omega-9 fatty acids serve as necessary components for other metabolic pathways, which may affect disease risk. These fatty acids which act as independent, yet synergistic lipid moieties that interact with other biomolecules within the cellular ecosystem epitomize the critical role of these fatty acids in homeostasis and overall health. This review focuses on the functional roles and potential mechanisms of omega-3, omega-6 and omega-9 fatty acids in regard to inflammation and disease pathogenesis. A particular emphasis is placed on cardiovascular disease, the leading cause of morbidity and mortality in the United States.
    [Show full text]
  • Thiazolidine-2,4-Dione Attenuates Atherosclerosis Possibly by Reducing Monocyte Recruitment to the Lesion
    EXPERIMENTAL and MOLECULAR MEDICINE, Vol. 43, No. 8, 471-478, August 2011 5-(4-Hydroxy-2,3,5-trimethylbenzylidene) thiazolidine-2,4-dione attenuates atherosclerosis possibly by reducing monocyte recruitment to the lesion Jae-Hoon Choi1,2*, Jong-Gil Park2,3*, Accepted 20 June 2011 Hyung Jun Jeon2, Mi-Sun Kim4, Mi-Ran Lee2, Available Online 21 June 2011 2 2 5 Mi-Ni Lee , SeongKeun Sonn , Jae-Hong Kim , Abbreviations: 5-LOX, 5-lipoxygenase; BHB-TZD, 5-(3,5-di- Mun Han Lee3, Myung-Sook Choi6, tert-butyl-4-hydroxybenzylidene) thiazolidin-2,4-dione; COX, Yong Bok Park7, Oh-Seung Kwon8, cyclooxygenase; HMB-TZD, 5-(4-hydroxy-2,3,5-trimethyl- Tae-Sook Jeong9, Woo Song Lee10, Hyun Bo Shim2, benzylidene) thiazolidin-2,4-dione; ICAM-1, intercellular 4 2,11 adhesion molecule-1; Ldlr, low density lipoprotein receptor; Dong Hae Shin and Goo Taeg Oh TNF-α, tumor necrosis factor-alpha; VCAM-1, vascular cell adhesion molecule-1 1Department of Life Science College of Natural Sciences Hanyang University Abstract Seoul 133-791, Korea 2Division of Life and Pharmaceutical Sciences A variety of benzylidenethiazole analogs have been Ewha Womans University demonstrated to inhibit 5-lipoxygenase (5-LOX). Here Seoul 120-750, Korea we report the anti-atherogenic potential of 5-(4-hy- 3 Department of Veterinary Biochemistry droxy-2,3,5-trimethylbenzylidene) thiazolidin-2,4-di- College of Veterinary Medicine one (HMB-TZD), a benzylidenethiazole analog, and its Seoul National University potential mechanism of action in LDL receptor-defi- Seoul 151-742, Korea cient (Ldlr-/-) mice. HMB-TZD Treatment reduced leuko- 4Division of Life and Pharmaceutical Sciences triene B4 (LTB4) production significantly in RAW264.7 College of Pharmacy macrophages and SVEC4-10 endothelial cells.
    [Show full text]